Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

Case of a palatal tic resembling palatal tremor in a patient with Tourette syndrome.

We describe a case of a palatal tic resembling palatal tremor (PT) in a young female patient with a previously unrecognized mild Tourette syndrome. At the time of her visit, the patient complained about ear clicks that were audible to others. We discuss the differential diagnoses of hyperkinetic palatal movements emphasizing the ongoing discussion about essential PT representing a more heterogeneous disorder than previously thought.     

Efficacy of transdermal clonidine for headache prophylaxis and reduction of narcotic use in migraine patients. A randomized crossover trial

Thirty patients completed a double-blind, randomized crossover study utilizing transdermal clonidine and an identical-appearing placebo. Crossover occurred at 6 weeks, with a total study time of 12 weeks. Subjects were asked to record daily in a special diary (1) the presence or absence of headache, (2) duration of headache, (3) severity of headache, and (4) use of pain medication for headache relief. The severity of the headaches was rated from 1 (very mild) to 5 (very severe). Although the subjects reported a decrease in frequency, duration, and intensity of headaches while using the medicated patch, these differences did not reach statistical significance. Nineteen patients subjectively preferred the medicated patch, while five preferred the placebo (P less than .01). During use of the medicated patch, a significant reduction (P = .039) occurred in use of class II narcotics. Three doses of these substances were used by the patients when treated with clonidine, while 34 doses were taken during placebo use. These findings suggest that clonidine might have a role in reduction of parenteral narcotic use in acute pain syndromes.     

Erinnerungen an traumatische Erlebnisse in der Zeit des Nationalsozialismus bei (ehemaligen) jüdischen Emigranten und Lagerhäftlingen

Zusammenfassung Halbstrukturierte Inteviews mit 248 (ehemaligen) jüdischen Emigranten und Lagerh?ftlingen in Deutschland und drei Ziell?ndern der jüdischen Emigration zeigen, da? Erinnerungen an traumatische Erlebnisse im Nationalsozialismus in zahlreichen allt?glichen Kontexten auftreten und von zentraler Bedeutung für die Wahrnehmung der pers?nlichen Lebenssituation im Alter sind. Auf der Grundlage der Ergebnisse einer Pilotstudie zur Frage nach der subjektiven Gliederung des Lebenslaufs bei (ehemaligen) jüdischen Emigranten und Lagerh?ftlingen werden unterschiedliche Abschnitte der pers?nlichen Entwicklung nach dem Holocaust unterschieden. Selbsteinsch?tzungen der Untersuchungsteilnehmer zur Intensit?t von Erinnerungen an traumatische Erlebnisse in diesen Entwicklungsabschnitten unterstützen die Annahme, da? belastende Erinnerungen im Alter deutlich zugenommen haben. Die Untersuchungsteilnehmer unterscheiden sich erheblich in den Formen der Auseinandersetzung mit solchen Erinnerungen. Einige Untersuchungsteilnehmer reagierten mit Depressionen, Angstzust?nden, Gefühlen von überlebensschuld und Rückzug aus sozialen Beziehungen. Andere engagierten sich hingegen in hohem Ma?e in sozialen Beziehungen, vor allem zu Angeh?rigen der jüngeren Generation, um dadurch zur Vermeidung von Diskriminierung, Rassismus und Fremdenfeindlichkeit beizutragen. Eingegangen: 14. August 1997, Akzeptiert: 26. Januar 1998     

Donor left ventricular hypertrophy increases risk for early graft failure

A review of factors contributing to early mortality after cardiac transplantation revealed that up to 25 % of deaths were due to primary graft dysfunction unrelated to rejection or infection. In light of this finding, evaluation of a donor heart with regard to its suitability for transplantation takes on added importance. In an effort to screen the suitability of donor hearts in the region covered by the Northwest Organ Procurement Agency (USA), all donors are evaluated by two-dimensional transthoracic echocardiography as part of the initial evaluation. A total of 110 donor echocardiograms were reviewed and an attempt was made to correlate the 30-day outcome with the parameters measured. An unexpected finding was that the presence of left ventricular hypertrophy in the donor heart was associated with an increase in the incidence of donor heart dysfunction compared with donors with normal echocardiographic profiles (33 % vs 3 %, P = 0.007). Received: 12 February 1996 Received after resision: 27 June 1997 Accepted: 14 July 1997     

92. Jahrestagung der Deutschen Gesellschaft für Kinderheilkunde und Jugendmedizin Begrüßung durch den Vorsitzenden

Ohne Zusammenfassung